Gsk Seroxat Death

8/9/2019 Gsk Seroxat Death

1/5

An Analysis of Use of Prozac, Paxil and Zoloft in USA 1988--2002

IMR US Sum 1.doc Page 1

The IMR Patient Flow Model has been used to analyse the usage of the SSRIs Paxil, Prozacand Zoloft in the US since each drug was introduced. The results for Paxil were given in an

open letter to Congressmen Barton and Greenwood (Ref.1). The letter also introduced theIMR Model and summarised its development and capabilities. This report will answer three

questions with results produced by IMR.

1 How many US patients have consumed these drugs since date of introduction ?

2) How many US patients have continued to use these drugs for many years ?

3) How many US patients may have been killed by drug induced suicide in the first weeks

of use ?

Numbers of Patients.

The IMR model starts in the year of introduction and uses specific Inman usage profiles for

each drug (Ref. 2) The known quantity of medication has been consumed by approximately

67.5M patients. Although it is possible that some patients may have switched betweendrugs and this would reduce the number of unique patients. Nevertheless a probable 8M

new SSRI patients in 2002 indicates the magnitude of the potential harm, particularly asthese drugs have little or no proven efficacy above placebo for the majority of conditions

for which they are now prescribed.

Table 1: New Patients on Prozac, Paxil and Zoloft.

Year

Prozac Paxil Zoloft Total

1988 899,856 899,856

1989 1,547,442 1,547,442

1990 1,947,338 1,947,338

1991 426,619 426,619

1992 1,787,521 213,790 2,001,310

1993 1,020,216 850,205 2,373,784 4,244,205

1994 2,863,022 1,467,859 1,677,421 6,008,302

1995 2,280,438 1,289,065 2,171,122 5,740,625

1996 2,328,614 1,653,982 1,940,201 5,922,796

1997 2,622,047 2,106,261 1,675,933 6,404,241

1998 2,663,209 2,037,645 2,106,666 6,807,520

1999 1,855,358 1,861,142 2,068,905 5,785,404

2000 1,380,479 2,330,549 2,292,718 6,003,747

2001 1,610,645 1,887,306 2,463,645 5,961,595

2002 1,805,015 3,046,058 3,041,536 7,892,609

Totals 27,037,820 18,530,071 22,025,721 67,593,612

New patients Starting on Drug in current year


2/5



Long Term Use

Although the majority of patients are forced to drop out during the first year of use, manypatients remain on SSRIs for many years, some out of choice, but some become dependant

and cannot withdraw. GSK have now been forced to admit that 25% (not 2% as they

previously claimed) of patients will have difficulty in withdrawing (June 2003).

Other long term patients confuse their drug induced withdrawal symptoms and believe that

these are their own original condition and that therefore the drugs must be making them

well. The lack of thoroughness of coroner investigations and the inadequacy of post-

mortem analyses means that there is no data to indicate how many suicides may be

triggered by attempted SSRI withdrawal. Table 2 presents the probable size of the long

term patient cohorts on each drug and their duration of dependence as at the end of 2002.

Table 2: Numbers of US patients in Long Term Use.

None of these drugs have ever been scientifically validated for such long term use either in

terms of efficacy or permanent central nervous system damage. The cost implications are

phenomenal. For example, the cost of keeping 2.163 million patients on these drugs for 7

years is over 20 billion dollars, (much of which are tax dollars). This money could have

funded alternative more effective and far less dangerous therapies. Table 2 is a snapshot at

the end of 2002, the whole picture is dynamic, the duration and cost of long term use will

continue to grow as time passes, Paxil and Zoloft are relatively young so their long term

populations and costs will increase.

This table illustrates the scope of IMR to analyse long term patient cohorts in detail for any

SSRI. New patients, drug induced harm and costs can all be derived from one coherentbase, founded on the published work.


1 year or more 2,831,468 2,565,975 2,894,978 8,292,421

3 Years or more 2,167,664 1,601,950 1,823,505 5,593,119

5 Years or more 1,669,161 945,426 1,142,992 3,757,579

7 Years or more 1,032,343 446,904 684,143 2,163,390

10 Years or more 382,243 57,483 173,215 612,941

12 Years or more 206,911 - - 206,911

Number of PatientsTime on Drug

Duration of use by US Long Term Patients as at end 2002


3/5



Drug Induced Suicides.

The IMR model uses some internal sequences to calculate the growing population ofpatients from the amount of medication that was consumed. But in order to calculate the

probable number of drug induced suicides it is necessary to have a suicide rate per given

number of patients at risk. This suicide rate must be provided externally and must relate toactual trials and studies, it cannot be generated by IMR. In view of the serious implications

of the tables 3 and 4 that follow, it is most important to briefly review the sources to give

provenance to the chosen rates.

All new patients or volunteers on SSRIs regardless of their mental condition, child or adult,

face a finite risk of drug induced suicide in excess of any risk of suicide that they had

before medication. GSK presented randomised clinical trial (RCT) results to the MCA for

Seroxat in 1990 in their UK licence application. This showed that Seroxat was 8 times more

likely to cause suicide or suicide attempts than placebo giving a rate of 236 suicides per

100K patients, zero for placebo. After some debate the application was withdrawn.

GSK then manipulated the results of the same trial, shifting suicides from Seroxat onto

placebo, and re-applied in 1991. The adjusted figures showed that placebo was now twiceas dangerous as Seroxat, giving a rate for Seroxat of 168 suicides/100K patients and an

incredible 361/100K for placebo. This affront to medical ethics, logic and common sensedid not dismay the MCA and on the basis of this data the MCA granted the lifetime UK

licence for Seroxat, which was never to be scientifically and critically reviewedsubsequently. This dangerous, inexplicable and incompetent approval in the UK

undoubtedly influenced the FDA to follow suit 2 years later when the Paxil licence was

granted.

In 1993, epidemiological studies (Ref.3) carried out by the Drug Safety Research Unit on a

cohort of 50 K patients who were using various SSRIs found gross rates of suicide as

follows:- 269 deaths/100Kfor Seroxat, 244/100K for Prozac and 173/100K for Zoloft. The

weighted average from the whole study is 219/100K. These gross figures must be reduced

by an estimate of suicides that might have occurred in that population if they had never

received medication. This additional data, provided by a study on 460K people over 5

years, suggests a cautious figure of 60/100K (Ref.4). The result is that the average SSRI

may typically cause at least 160/100K suicides in excess of the suicides that may occur

without medication.

Both clinical and epidemiological studies suggest that it would be quite justifiable to runIMR with an average SSRI induced suicide rate of about 160/100K. However, in theinterests of careful science and caution, a range of excess rates between only 32 to 104 drug

induced suicides per100K patients has been chosen to predict the range of total druginduced deaths. To put it another way, the results have been calculated using rates of one

fifth to three fifths of the excess induced suicide rates that have been measured in actual

clinical trials and epidemiological studies on SSRIs.

Although all SSRI patients are at risk of induced suicide and other harm at every dose

transition (starting, stopping and increasing dose) the drug induced withdrawal suicides and

mid treatment dose change suicides are not included in this analysis.


4/5



Table3 (Below): Drug Induced Suicides in the US ( rate of 32/100K patients )

Table 4 (Below): Drug Induced Suicides at rate of 104/100K patients.

YearProzac Paxil Zoloft Total

1988 292 292

1989 501 501

1990 631 631

1991 138 138

1992 579 69 648

1993 331 275 769 1,375

1994 928 476 543 1,947

1995 739 418 703 1,860

1996 754 536 629 1,919

1997 850 682 543 2,075

1998 863 660 683 2,206

1999 601 603 670 1,874

2000 447 755 743 1,945

2001 522 611 798 1,932

2002 585 987 985 2,557

Totals 8,760 6,004 7,136 21,900

Excess (Drug Induced) Suicides

32 deaths per 100K new patients

Year


1988 936 936

1989 1,609 1,609

1990 2,025 2,025

1991 444 444

1992 1,859 222 2,0811993 1,061 884 2,469 4,414

1994 2,978 1,527 1,745 6,249

1995 2,372 1,341 2,258 5,970

1996 2,422 1,720 2,018 6,160

1997 2,727 2,191 1,743 6,660

1998 2,770 2,119 2,191 7,080

1999 1,930 1,936 2,152 6,017

2000 1,436 2,424 2,384 6,244

2001 1,675 1,963 2,562 6,200

2002 1,877 3,168 3,163 8,208

Totals 28,119 19,271 22,907 70,297

104 deaths per 100K new patients

Excess (Drug Induced) Suicides


5/5



Table1 shows that, in 2002, 7.8 million Americans became new users of either Paxil,

Prozac or Zoloft and therefore they faced a net risk of induced suicide that is not likely tobe lower than 32/100K and very probably is higher than 104/100K. Nevertheless, even

using these cautionary rates, somewhere between 2500 and 8200 excess suicides may have

occurred in 2002 alone due to these drugs.

Whatever the value of the suicide rate, it was not zero. At least two thousand Americans

may have died in 2002 who were not warned of the possible lethal outcome of their SSRI

medication. This is the consequence of a dysfunctional drug safety regulation system in

which the drug manufacturers have not only failed to disclose evidence of great harm but

also have infiltrated virtually every organisation that could criticise, study and report on

their drugs with scientific objectivity. This is compounded by the doctors who continually

fail in their duty to report possible adverse effects, (i.e. suicide within days of starting the

drug), associated with the dangerous drugs that they prescribe so frequently and so readily

for virtually all the problems of life, culture and society.

But the spotlight must now fall on the FDA (together with the other national regulators,) to

explain why it has been so unreactive, unaware and in such positive denial of the possibleharm and deaths caused to the American population by the drugs that it has approved since

1988.

The significance of this paper is that for the first time some credible numbers are availableto assist the FDA who confidently assert, without any knowledge of the number of patients

at risk and the extent of harm that the benefits of the drug outweigh the harm . Now with

the IMR results harm/ benefit ratios can be discussed scientifically and three very serious

questions can be asked.

1) What processes have the FDA used to measure the benefit for SSRI drug users?.

2) How many units of benefit equate to one drug induced suicide ?

3) How many drug induced suicides will the FDA toleratebefore robust regulatory

intervention is provoked ?

Graham Aldred 6 June 2004

[email protected]

Ref1: Open Letter to Congressmen Barton and Greenwood Number of US Citizens at risk to SSRIs :

Graham Aldred : 27 April 2004.

Ref2: PEM Report No .6: Paroxetine : William Inman et al : 1993: Pharmacoepidemiology & Drug Safety:

Vol 2 393-422.

Ref3: A Comparison of paroxetine etc by observational cohort studies. FJ MacKay et al: 1997:

Pharmacoepidemiology & Drug Safety: Vol 6 : Supp 3: 5-11.

Ref 4 Modelling Suicide Risk in Affective Disorders: A P Boardman & D Healy: 2001: Eur. Psychiatry vol

16: 400-5.

Gsk Seroxat Death

Documents

Transcript of Gsk Seroxat Death